Why science reporters should do their homework

One of the most significant medical advancements of the last few decades has been the use of cholesterol-lowering medications called statins. These drugs, when used properly, have been shown over and over to lower the risk of heart attacks, strokes, and death. But like all drugs, they have many effects, both those we like (preventing heart attacks) and those we don’t (in this case, rare liver and muscle problems); the latter we call “side-effects”. Studies done on drugs before they hit the market can identify common side-effects, but it’s not until many more people are exposed for a long period of time that rare side-effects show up.

A recent Scientific American article wondered if one of these rare side-effects could be memory problems. At first glance, the idea seems pretty improbable, but the SI article takes some sketchy anecdotes and runs with the idea, managing to cobble together an interesting hypothesis:

It is not crazy to connect cholesterol-modifying drugs with cognition; after all, one quarter of the body’s cholesterol is found in the brain. Cholesterol is a waxy substance that, among other things, provides structure to the body’s cell membranes. High levels of cholesterol in the blood create a risk for heart disease, because the molecules that transport cholesterol can damage arteries and cause blockages. In the brain, however, cholesterol plays a crucial role in the formation of neuronal connections—the vital links that underlie memory and learning. Quick thinking and rapid reaction times depend on cholesterol, too, because the waxy molecules are the building blocks of the sheaths that insulate neurons and speed up electrical transmissions.

It’s not crazy to connect cholesterol-modifying drugs with cognition, but it’s quite a stretch. We do know that statins affect the central nervous system. They’ve been proven to reduce the risk of stroke, a devastating central nervous system disease. If they can prevent brain disease, might they also cause it? We have some ideas about why statins prevent strokes: they lower cholesterol and stabilize arterial plaques, perhaps by reducing inflammation in these plaques. They can even cause plaques in some arteries to shrink. Is there a plausible hypothesis as to why statins might cause memory problems? What is being posited is that statins actually reduce cholesterol levels so much that cell membranes are damaged and neuronal saltatory conduction* is impaired. If this were the case, we might also expect to find cognitive differences when comparing people with high and low cholesterol levels, or to see cognition affected by cholesterol-lowering diets. This is not the case.

Still, dementia—the most common and severe form of memory loss— is a devastating disease, so if there is even a chance, maybe we should ask the question. A large cohort study published in Archives of Neurology in 2005 looked into whether statins might actually help prevent dementia. They groups of elderly patient who took statins, and those who did not and compared the incidence of dementia in each group. There found neither a protective effect nor a harmful effect.

The idea that lipids (fat molecules) can affect brain function has been supported by certain epidemiologic studies and some animal models. Omega-3-fatty acids have been touted for possible use in preventing and treating dementia. Last week, a randomized controlled trial of a particular omega-3-fatty acid was published in JAMA. The study design was strong, and the study found no evidence that this particular molecule helped dementia patients.

The two most common types of dementia are vascular dementia and Alzheimer’s disease. The cause of Alzheimer’s disease isn’t known, making prevention difficult. Vascular dementia, however, is to a certain extent preventable. It is caused by a variety of factors that affect blood vessels such as hypertension, and studies have shown that many of the same interventions that prevent stroke can help prevent vascular dementia. One of the most potent risks for vascular disease is cigarette smoking, so it would make sense that smoking would be a risk factor for vascular dementia. A surprising result of a study recently published in Archives of Internal Medicine was that smoking is a risk factor not only for vascular dementia but also for Alzheimer’s dementia.

The story of dementia risk is complex, and there is a rich vein of literature to mine. I was disappointed that the SI article presented anecdotes rather than data, case-reports rather than good studies, and highlighted “experts” who presented fear-mongering testimony rather than the measured caution that we can expect from real experts.

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*“Saltatory conduction” describes a way that nerve signals travel quickly. Nerve cells can function as a sort of wire for electrical signals, and the myelin sheath allows electrical signals to jump from node to node, increasing the speed of conduction when compared to an un-myelinated neuron. Certain diseases, such as multiple sclerosis, involve destruction of the myelin sheath, decreasing nerve conduction velocity, leading to weakness and other symptoms. Myelin contains cholesterol, among other things.

9 Comments

Does degrading the myelin actually disrupt neuronal function? I mean theoretically the AP should be able to continue to propigate itself, just not as quickly. I suppose that could cause loss of synchronization, etc. (Note: I’m not a neurobiologist so this may be a question with an easy answer.)

PalMD

Kierra

In my neuro classes, it was explained that the action potential propagates by voltage spread where the myelin sheath is and then kick-starts another AP at each node. It was implied that the voltage would decay too much to start the next AP if the myelin sheath wasn’t there. But since in was introductory neurobiology, that may have been a simplification.

GoatRider

PalMD

GoatRider

Brad

IANAD and can’t vouch for my memory or the study it remembers, but I do remember hearing at some point that the rate of Alzheimer’s in smokers was lower than in non-smokers. I’m interested in seeing the data.

From what I know of Alzheimer’s and nitric oxide, I suspect the effects are complex. Carbon monoxide does have some cross-talk with NO, and so CO might have some acute protective effects. However exposure to CO likely programs a low-NO setpoint (to counter the high CO/NO cross-talk).

People who smoke, do so to deal with nicotine addiction, not to deliver therapeutic CO levels. There is other crap in tobacco smoke that does cause oxidative stress which lowers NO levels. Nicotine does raise NO levels too, but that most likely causes compensatory down-regulation of NOS expression and it is that down regulation that likely causes the adverse cardiovascular effects of nicotine.

Smoking does tend to make cardiovascular stuff worse. It would very likely make Alzheimer’s worse too. Any hypothetical protective effect of CO would be acute, and would be highly dose dependent, and the needed dose would change over time and would not be easily determined.

The data on smoking and Alzheimer’s doesn’t have the resolution to sort out these different effects which are likely idiosyncratic and dose-dependent. The vast majority of the data on health effects of smoking says smoking is bad for cardiovascular stuff, that would make it bad for Alzheimer’s and all the other neurodegenerative diseases.